# ANTIIDIOTYPIC REGULATION OF AUTOIMMUNE DISEASE

> **NIH NIH R01** · UNIVERSITY OF MARYLAND BALTIMORE · 1988 · $154,630

## Abstract

Data from many laboratories suggest that autoimmunity results from an
imbalance in normal immunoregulation.  Jerne first hypothesized that
immunological reactivity was regulated by an intricate network involving
idiotype-antiidiotype (id-antiid) interactions.  If autoantibody production
is normally regulated by a network of id-antiid interactions, then
autoimmunity may result from an alteration in that network.  We propose to
examine the network theory in the clinically-relevant antierythrocyte
antibody (aRBC) autoimmune disease of NZB mice.  This autoantibody response
provides a unique opportunity to dissect the id-antiid network in
autoimmunity, since it is an oligoclonal response, organ specific and
easily measured.  We have produced a large panel of monoclonal NZB aRBC
antibodies.  The specific aims of the proposal are to use oour established
monoclonal aRBC and monoclonal antiid antibodies to determine whether:

1) the production of aRBC in NZB mice is associated with an alteration in
anti-idiotypic immunoregulation;

2) the immune network can be perturbed to the benefit of the NZB mouse by
administration of antiid antibodies directed against the ids present on NZB
aRBC, with subsequent specific down-regulation of id expression and
remission of the autoimmune disease;

3) initial down-regulation is followed by recurrence of disease due to the
appearance of escape ids, anti-antiid (Ab3) antibodies or id-antiid immune
complex renal disease; and

4) recurrence, if it occurs, can be prevented by altering the type or dose
of antiid antibody administered, or the combined use of antiid antibodies
and cytotoxic drugs.

If the administration of antiid antibodies to NZB mice results in the
down-regulation of id expression and amelioration of autoimmune hemolytic
disease, this research will have major implications relative to the
understanding of the underlying immune defects in NZB mice and provide a
model for the treatment of autoimmune disease in man, an approach which
offers the possibility of highly specific immunosuppression of pathogenic
autoantibody production.

## Key facts

- **NIH application ID:** 3158257
- **Project number:** 5R01AR037628-03
- **Recipient organization:** UNIVERSITY OF MARYLAND BALTIMORE
- **SAM.gov UEI:** Z9CRZKD42ZT1
- **Principal Investigator:** BARRY S. HANDWERGER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1988
- **Award amount:** $154,630
- **Award type:** 5
- **Project period:** 1986-01-01 → 1989-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3158257

## Citation

> US National Institutes of Health, RePORTER application 3158257, ANTIIDIOTYPIC REGULATION OF AUTOIMMUNE DISEASE (5R01AR037628-03). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3158257. Licensed CC0.

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